Dissecting the circuitry of dopaminergic projections to the striatum with Cholera Toxin B

Abstract

The objective of this senior thesis project is to elucidate anatomical distinctions between dopaminergic projections from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) to the dorsomedial striatum (DMS) and nucleus accumbens (NAc). Despite their anatomical proximity, the functional identities of the DMS and the NAc are distinct in several ways—one notable example is their proposed roles in the actor-­‐critic model of instrumental conditioning. A potential contributor to such a dichotomy is the spatial profile of the dopaminergic projections that each region receives from the VTA and SNc, yet this notion has not been clarified by careful anatomical investigation. Cholera toxin B is a subunit of cholera toxin that has been repurposed through bioengineering to be a sensitive retrograde tracer. As such, it can be injected into a region of interest and will travel up axons, labeling any neuron with terminals at the injection site. In this study, we used fluorescently-­‐tagged cholera toxin B to examine the source of the dopaminergic innervation of the DMS and NAc on a cellular level, in order to determine to what extent the same dopamine neurons innervate each area. We found that dopaminergic neurons that project to the DMS are fairly intermingled spatially with those that project to the NAc, but also that 92% of observed dopaminergic CTB-­‐ labeled neurons independently project to only one of these regions. This significant cellular independence could contribute to the pathway-­‐dependent functionality of dopamine observed the DMS and NAc, and may be indicative of a larger trend in dopamine signaling.